Scientists, doctors, and others have long suspected that a person on effective antiretroviral treatment that reduces HIV to an undetectable level would be significantly less likely to infect a sexual partner. Viral load in the blood and genital tract are correlated with risk of infection, and typically HIV levels are concordant between plasma and the genital tract (although there is little research on this topic).

This is true with most infectious diseases: the amount of infectious material -- called microbial load -- is strongly predictive of the risk of person-to-person transmission. Additionally, several observational studies have found that people on HIV treatment are less likely to transmit the virus sexually than those not on treatment.

Nevertheless, the concept of "treatment as prevention" has remained somewhat controversial. Many people have been hesitant to fully embrace this idea. One of the main reasons has been the lack of evidence from prospective, randomized, controlled clinical trials -- the gold standard of biomedical research. Results from just such a trial have now been reported. These findings are unequivocal and have the potential to shift the course of the AIDS pandemic.

In an oral session at IAS 2011, Myron Cohen from the University of North Carolina presented top-line results from HPTN 052, a large, randomized, controlled clinical trial examining the effect of antiretroviral treatment on the risk of sexual transmission of HIV. Results were published simultaneously in the New England Journal of Medicine.

The study enrolled 1763 couples in 9 countries on 4 continents. Over half the participants were in sub-Saharan Africa, where the epidemic is most widespread and where the most commonly circulating clade of HIV is thought to be the most infectious.

All couples were serodiscordant, meaning 1 partner was HIV positive and the other HIV negative. At enrollment the HIV positive person had to be ineligible for antiretroviral therapy based on their county’s treatment guidelines. Couples were randomized to 1 of 2 groups:

Immediate treatment -- the HIV positive person started antiretroviral therapy at the time of enrollment;

HPTN 052 had 2 primary objectives. First, it examined rates of linked infections, meaning a new infection that could be genetically matched to virus from a partner. This was important because it was assumed that some people in the study would have sexual contact outside of their primary relationship. The second objective was comparing clinical outcomes for HIV positive participants in the immediate versus delayed arms. The clinical outcome results will be covered in a separate report.

Results

A total of 39 new HIV infections occurred during the study: 4 in the immediate arm and 35 in the delayed arm.

Of those, there were 28 linked transmissions: 1 in the immediate arm and 27 in the delayed arm.

Overall, there was a 96% reduction in transmission in the immediate compared with the delayed arm.

The rate of linked new infections was 0.1 per 100 person years (PY) in the immediate arm vs 1.7 per 100 PY in the delayed arm.

The overall rate of new infections was 0.3 per 100 PY in the immediate arm compared to 2.2 per 100 PY in the delayed arm.

Rates of other sexually transmitted infections were similar between arms.

Reported frequency of sexual contact was similar between arms.

Self-reported condom use was high overall (greater than 90%) and similar in both arms.

On April 28, 2011, the study’s independent Data Safety and Monitoring Board (DSMB) recommended making these results public. The DSMB felt the effectiveness of treatment in preventing new infections meant it would be unethical not to share this information with study participants. The study also decided to offer antiretroviral treatment to all HIV positive members of the couples. The trial was originally meant to last until 2015 and it will continue in order to measure the durability of the prevention effect.

The authors of the study emphasized that treatment as prevention should be seen as part of a comprehensive combination prevention effort that includes other biomedical interventions such as vaginal and anal microbicides, as well as behavioral interventions like condoms and clean needles.

The HPTN 052 findings are remarkable results. The effect observed in this trail is significantly larger than with other biomedical approached studied thus far. For comparison, there have been several studies of PrEP that have shown reductions in new infections between 0% and 78%. HIV vaccine protection rates have topped out at around 40% in various studies.

While these results are exciting, it is important to point out that even in the U.S. most people with HIV have do not have undetectable HIV viral load because they do not know their HIV status, are not on treatment, or are not on fully suppressive therapy.

The lack of universal access to HIV treatment and testing -- both in the U.S. and more so throughout the developing world -- will likely blunt the real-world impact of these findings. Treatment as prevention can only work if people know they have HIV and if they have access to treatment. Expanding access to HIV treatment and testing will be crucial to maximizing the effect of this powerful tool against HIV.